For example, expression of CHAIRY1 spreads along the presomitic mesoderm during the formation of each somite [4]. DeltaNotch is a key cascade pathway in somatogenesis and in the regulation of the “segmentation clock.” This complex process can be simplified as follows: Notch active Lunatic Fringe which in turn inhibits the Notch receptor. Activation of Notch also stimulates activation of the HES gene which inhibits Lunatic Fringe, releasing the Notch receptor. This genetic feedback allows the cyclic expression of these genes. In humans, mutations of LFNG genes (Lunatic Fringe), HES7 (Hairyenhancer of split7), DLL3 (encoding for the Notch ligand), and MESP2 (activated Notch) are responsible for recessive forms of spondylocostal dysostoses (Fig. 2).

The positional identity of somites according to the cephalocaudal axis is defined by a combined expression of genes encoding transcription factors and belongs to the family of HOX (homeotic) genes. This specification occurs in the presomitic mesoderm prior to somitogenesis. The HOX genes are grouped into several complexes on the chromosomes. The genes of each complex are expressed sequentially in a spatial and temporal order defined by their position along the chromosome. In Drosophila, there is only one HOX gene complex (initially called the HOM complex). Thus, the loss of function of one of these genes leads to a homeotic transformation in the adult insect, transforming an entire part of the body into another. In mammals, there are four HOX gene complexes on four different chromosomes. In mice, experiments have shown that inactivation of different HOX gene complexes resulted in the appearance of different phenotypes, frequently comprising vertebral malformations. In humans, no vertebral malformations have been linked to mutations in HOX gene complexes [5].

Embryology of the Vertebromedullary Axis

Early Development

The embryonic period is defined as the first 8 weeks after fertilization. During the first week after fertilization, the morula migrates along the fallopian tube. At the end of the first week, the morula became a blastocyst following the appearance of a cavity, the blastocele (Fig. 3). It is at this time that implantation takes place in the maternal uterine mucosa (Fig. 4). At this stage, the embryonic disc is transformed into a bilaminar structure, comprising two layers, the epiblast and the hypoblast. At the beginning of the third week, a primitive streak appears in the middle of the epiblast and gradually lengthens. The craniocaudal axis of the embryo that forms during the primitive streak extends from the primitive node which determines the cranial end of the embryo (Fig. 5).

Trilaminar Embryo

The third week is marked by gastrulation. The epiblastic cells migrate from the deep side of the primitive streak and the hypoblast is laterally displaced to contribute to the formation of the extraembryonic endoderm. The migration of the epiblastic cells through the primitive streak and the node leads to the formation of the three primordial germ layers: the definitive endoderm which takes the place of the hypoblast, the ectoderm that remains on the surface, and the mesoderm which lies in between.

The axial mesoderm consists of two median structures: the prechordal plate and the notochordal process. The prechordal plate, situated at the cranial extremity, is adherent to the ectoderm, whereas the notochordal process is situated more caudally and is transformed into a tubular structure, causing the yolk sac (this structure gives rise exclusively to extraembryonic structures) and the amniotic sac to communicate transiently. This communication is called the notochordal (or chordal) canal (of Lieberkühn).

Three lateral structures appear on either side of the embryo: the paraaxial mesoderm (Fig. 6), the intermediate mesoderm, and the lateral mesoderm. The paraaxial mesoderm gives rise to cell lines that differentiate into an axial skeleton, paravertebral muscles, dermis, and subcutaneous tissue and muscles of the ventral wall and limbs. The intermediate mesoderm will be the origin of the urogenital tract. The ventral part of the lateral mesoderm will form the walls of the digestive tract and of the bronchopulmonary tree, while its dorsal part will form the lateral and ventral walls of the embryo.